The unifying goal of this program project proposal is to define the principles governing normal nervous system developmental processes that may lead to brain dysfunction and mental retardation. The studies for the most part are basic in nature, focusing on various aspects of the cell and its environment that are involved in overall developmental processes; including examination of the extracellular matrix (ECM), cell membrane gap junctions, cytoskeletal proliferation. The derivative information from these proposed studies should define specific loci where normal developmental processes. The first project focuses on the structure and function of brain proteoglycans. The emphasis is on control of one of the major chondroitin sulfate proteoglycans (aggrecan) and elucidation of the role this important ECM component plays in neuronal development. The second project will examine intracellular communication which may play a significant role in embryonic neural development by specifically studying Connexin45, a subunit gap junction protein with special permeability properties. The third project focuses on function of NF1 protein in central nervous system neurons and astrocytes using a combination of biochemical, molecular biology and confocal microscopy techniques in tissue culture models from the chick embryos and human CNS cell lines. The fourth project is aimed toward understanding the pathogenesis of Batten disease. The aim is to develop diagnostic biochemical assays for the enzymes deficient in CLN2 (PPT) and CLN2 (endoprotease) and to determine the cause of neuronal death. A comprehensive multi-disciplinary approach using biochemical, molecular, morphologic and cell culture techniques will be used in all four projects.